4-(4-(3,4-dimethoxybenzyl)-piperazin-1-yl)phenylamine | 927998-99-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-(4-(3,4-dimethoxybenzyl)-piperazin-1-yl)phenylamine
• 英文别名: 4-[4-[(3,4-Dimethoxyphenyl)methyl]piperazin-1-yl]aniline
• CAS: 927998-99-0
• 化学式: C₁₉H₂₅N₃O₂
• 分子量: 327.426
• InChiKey: RQXORXRWLVVNAT-UHFFFAOYSA-N

物化性质

• 熔点：
  120-121 °C
• 沸点：
  500.4±50.0 °C(Predicted)
• 密度：
  1.163±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  51
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(4-(3,4-dimethoxybenzyl)-piperazin-1-yl)phenylamine 在 potassium carbonate 、 1-羟基苯并三唑 、 对甲苯磺酸甲酯 作用下， 以 二氯甲烷 为溶剂， 反应 72.0h， 生成 N-(2-((4-(4-(3,4-dimethoxybenzyl)piperazin-1-yl)phenyl)carbamoyl)-4,5dimethoxyphenyl)quinoline-3-carboxamide
  参考文献：
  名称：

  In vitro activity of novel dual action MDR anthranilamide modulators with inhibitory activity on CYP-450 (Part 2)

  摘要：

  Synthesis and in vitro cytotoxicity assays of new anthranilamide MDR modulators have been performed to assess their inhibition potency on the P-glycoprotein (P-gp) transporter. Previous studies showed that the replacement of the aromatic spacer group between nitrogen atoms (N-1 and N-2) in the P-gp inhibitor XR9576 with ethyl or propyl chain is optimal for P-gp inhibition potency. To confirm that observation, the ethyl or the propyl linker arm was replaced with a pyrrolidine or an alicyclic group such as cyclohexyl. In addition, an arylpiperazinyl group and two methoxyl groups onto the anthranilic part were introduced to assess their effect on the anti P-gp activity. Five molecules were prepared and evaluated on CEM/VLB500. All new anthranilamides were more potent than verapamil, most of them exhibited a lower cytotoxicity than XR9576. Compound 5 was the most potent and its inhibition activity was similar to XR9576. Interestingly, in vitro biotransformation studies of compounds 4 and 5 using human CYP-450 isoforms revealed, that conversely to XR9576, compounds 4 and 5 inhibited CYP3A4, an enzyme that colocalizes with P-gp in the intestine and contributes to tumor cell chemoresistance by enhancing the biodisposition of numerous drugs, notably paclitaxel. In that context, 5 might be suitable for further drug development. (C) 2007 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2007.03.014
• 作为产物：
  描述：

  1-(4-硝基苯基)哌嗪 在 palladium 10% on activated carbon 、 氢气 、 溶剂黄146 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 0.5h， 生成 4-(4-(3,4-dimethoxybenzyl)-piperazin-1-yl)phenylamine
  参考文献：
  名称：

  一种含氮杂环衍生物及其应用

  摘要：

  一种含氮杂环衍生物及其应用。本发明涉及式(V)化合物和制备方法及其在医药上的应用。具体而言，本发明涉及通式为(V)化合物的衍生物和制备方法以及其作为治疗剂，在预防和治疗高脂血症，高胆固醇血症，高甘油三酯血症，肝脂肪变性，II型糖尿病，高血糖症，肥胖症或胰岛素抵抗症，代谢综合征和抗肿瘤药物中的用途。本文公开的化合物还能降低总胆固醇，LDL‑胆固醇和甘油三酯，并且增加肝LDL受体表达，抑制PCSK9表达。

  公开号：

  CN107540636A

文献信息

• In vitro activity of novel dual action MDR anthranilamide modulators with inhibitory activity on CYP-450 (Part 2)
  作者：Philippe Labrie、Shawn P. Maddaford、Jacques Lacroix、Concettina Catalano、David K.H. Lee、Suman Rakhit、René C. Gaudreault

  DOI：10.1016/j.bmc.2007.03.014

  日期：2007.6.1

  Synthesis and in vitro cytotoxicity assays of new anthranilamide MDR modulators have been performed to assess their inhibition potency on the P-glycoprotein (P-gp) transporter. Previous studies showed that the replacement of the aromatic spacer group between nitrogen atoms (N-1 and N-2) in the P-gp inhibitor XR9576 with ethyl or propyl chain is optimal for P-gp inhibition potency. To confirm that observation, the ethyl or the propyl linker arm was replaced with a pyrrolidine or an alicyclic group such as cyclohexyl. In addition, an arylpiperazinyl group and two methoxyl groups onto the anthranilic part were introduced to assess their effect on the anti P-gp activity. Five molecules were prepared and evaluated on CEM/VLB500. All new anthranilamides were more potent than verapamil, most of them exhibited a lower cytotoxicity than XR9576. Compound 5 was the most potent and its inhibition activity was similar to XR9576. Interestingly, in vitro biotransformation studies of compounds 4 and 5 using human CYP-450 isoforms revealed, that conversely to XR9576, compounds 4 and 5 inhibited CYP3A4, an enzyme that colocalizes with P-gp in the intestine and contributes to tumor cell chemoresistance by enhancing the biodisposition of numerous drugs, notably paclitaxel. In that context, 5 might be suitable for further drug development. (C) 2007 Published by Elsevier Ltd.
• 一种含氮杂环衍生物及其应用
  申请人：成都贝斯凯瑞生物科技有限公司

  公开号：CN107540636A

  公开（公告）日：2018-01-05

  一种含氮杂环衍生物及其应用。本发明涉及式(V)化合物和制备方法及其在医药上的应用。具体而言，本发明涉及通式为(V)化合物的衍生物和制备方法以及其作为治疗剂，在预防和治疗高脂血症，高胆固醇血症，高甘油三酯血症，肝脂肪变性，II型糖尿病，高血糖症，肥胖症或胰岛素抵抗症，代谢综合征和抗肿瘤药物中的用途。本文公开的化合物还能降低总胆固醇，LDL‑胆固醇和甘油三酯，并且增加肝LDL受体表达，抑制PCSK9表达。